Alzheimer's disease can be latent for 20 years before the onset of disease. Two major measures can help you prevent its progression!

*Only for medical professionals to read for reference AD ​​pre-clinical intervention methods include drug therapy and non-drug therapy, both of which should be paid attention to
.

Recently, the 2021 Alzheimer's Disease (AD) Prevention and Control Hotspot Seminar was held online
.

At the meeting, Professor Han Ying from Xuanwu Hospital of Capital Medical University shared the pre-clinical drug and non-drug therapies of AD
.

Let's learn together! AD is divided into 6 stages, and the pre-clinical stage can be latent for 20 years! The prevalence of AD dementia in China is increasing year by year
.

According to an article published in The Lancet Public Health in 2020, among the elderly people over 60 years old in China, AD population accounted for 3.
94% (10.
4 million), vascular dementia accounted for 1.
57% (3.
92 million), and other dementia accounted for 0.
53% (1.
32 million).
, Mild cognitive impairment (MCI) was 15.
5% (38.
77 million)
.

Behind these huge numbers are the heavy financial burdens and mental torture of countless families
.

Figure 1 The prevalence of different types of dementia in China Figure 2 The relationship between the prevalence of dementia and age At present, according to the latest international standards in 2018, AD is divided into 6 stages
.

Stage 1: Only amyloid (Aβ) is positive; Stage 2: Subjective cognitive decline (SCD) occurs; Stage 3: MCI; Stage 4: AD1, mild AD dementia; Stage 5: AD2, moderate AD dementia; Stage 6: AD3, severe AD dementia
.

Among them, the first two stages are collectively referred to as the preclinical stage of AD, and this "incubation period" can be as long as 20 years
.

The most important thing for AD prevention and treatment is early detection.
If timely intervention in the pre-clinical stage, the patient can remain in the pre-clinical stage for life without progress and ensure the quality of life
.

However, there was no intervention drug in the preclinical stage of AD before
.

It was not until the advent of the original domestically-developed drug Mannite Sodium in December 2019 that this gap was filled
.

On June 7 this year, the U.
S.
Food and Drug Administration (FDA) also approved the listing of monoclonal antibody drugs targeting amyloid for the treatment of AD for the preclinical treatment of AD
.

There is finally medicine to cure AD in the preclinical stage! At the stage of AD dementia, treatment drugs include cholinesterase inhibitors, N-methyl-D-aspartate (NMDA) receptor antagonists, etc.
, but they can only improve symptoms, delay the progression of the disease, and cannot reverse the condition.
Compared with pre-clinical treatment, the efficacy is greatly reduced
.

In the pre-clinical stage of AD, there is finally strength to send new drugs.
The pathological mechanism of AD is complicated, and the current treatment drugs are often only for a single target, which may be an important factor that causes the poor efficacy of existing drugs
.

Therefore, in order to achieve a breakthrough in AD treatment, a comprehensive, multi-target treatment strategy is required
.

The classic treatments for AD include donepezil, rivastigmine and memantine, which are all transmitter replacement therapies
.

As mentioned above, these drugs cannot prevent or even reverse the process of AD, leading the public to misunderstand that "AD cannot be prevented and cannot be treated"
.

In fact, the "senile plaques" in the brains of AD patients-amyloid plaques-appeared as early as 20 years before the onset of clinical symptoms, so treatment at this stage is very important
.

At present, with the help of mannite sodium and other drugs, it has been possible to treat AD in the preclinical stage
.

According to the research results of Professor Geng Meiyu in 2019, during the onset of AD, the composition of the intestinal flora will change, causing abnormal metabolites, stimulating peripheral immune cells Th1 to infiltrate the brain, activating M1 type microglia in the brain, and causing AD Related neuroinflammation leads to a decline in cognitive function
.

Mannat sodium can reshape the intestinal flora, inhibit abnormal metabolites, prevent peripheral inflammatory immune cells from infiltrating the brain, reduce neuroinflammation, and at the same time inhibit Aβ deposition and Tau protein phosphorylation, so as to achieve the purpose of treating AD
.

At present, this drug has been used in clinical practice in China and received good feedback
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There are many ways to prevent AD without taking medicine.
In recent years, non-pharmacological intervention measures for the SCD stage of AD preclinical stage have also been explored clinically
.

Dr.
Sheng Can of Professor Han's research group conducted a systematic review and Meta analysis of non-pharmaceutical interventions in the SCD stage, and the results showed that the intervention at this stage is effective
.

Non-pharmaceutical interventions in the SCD stage have benefits such as avoiding drug side effects and giving full play to cognitive reserves, and the SCD stage is highly heterogeneous.
Non-pharmacological interventions can cover various types of SCD and have a broader effect
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Interventions include probiotics, functional foods, cognitive training, life>
.

The role of intestinal microbes in the course of AD has been paid more and more attention in recent years
.

The mechanism of intestinal flora imbalance leading to AD may include: intestinal flora imbalance causes an increase in pro-inflammatory factors, lipopolysaccharides, etc.
, which destroys intestinal permeability, thereby increasing the content of systemic circulating microorganisms, microbial products and inflammatory factors, and further destroying the blood-brain barrier , Causing central nervous system (CNS) inflammation and neurodegeneration; imbalance of intestinal flora causes an increase in Aβ accumulation in the enteric nervous system, which leads to an increase in Aβ in the CNS, causing neuroinflammation and neurodegeneration; microbial products in the systemic circulation can also promote Aβ deposition in CNS
.

Stool testing found that the types and numbers of intestinal microbes in AD patients have changed, such as a decrease in the content of bifidobacteria and an increase in Bacteroides
.

Professor Han Ying’s group also found that compared with normal controls, the anti-inflammatory gut microbial abundance in SCD population was significantly reduced
.

The development and utilization of microbial drugs can help optimize individual flora.
For example, plant lignans can improve human immunity by optimizing intestinal flora
.

Cognitive intervention mainly refers to the direct or indirect treatment of cognitive function by non-drug intervention, including cognitive stimulation, cognitive rehabilitation and cognitive training
.

A study on mice found that physical exercise and cognitive training played an effective role in protecting cognitive function, reducing the damage of Aβ toxicity to memory, tissue oxidative stress, and hippocampal structure damage; another study showed that cognition Training can improve cognitive function and mood disorders at the same time
.

Unhealthy life>
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Restoring a healthy life>
.

It is recommended to quit smoking, exercise regularly, eat a reasonable diet, and drink moderately
.

In addition, special attention should be paid to low-sugar and low-fat diet.
Studies have shown that high-sugar and high-fat intake can change the types of intestinal microbes, cause intestinal dysfunction, and even lead to cognitive decline
.

Aluminum intake and low vitamin D levels are related to the increased risk of dementia.
Unsaturated fatty acids, antioxidants, vitamin B, and the Mediterranean diet can help reduce the risk of dementia
.

Studies have shown that cognitive function is regulated by biological rhythms and non-visual effects of light, and the regulation of light on cognition is affected by light time, photon density and wavelength
.

In 2019, Professor Han Ying's research group carried out a study on non-pharmaceutical intervention therapy of light stimulation for SCD population and normal elderly, and found that light therapy is effective in improving the cognition of the elderly
.

Music and dance have a strong and benign effect on AD patients, and can improve the quality of life of patients by providing memory stimulation, emotional regulation and social interaction
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In addition, in response to some of the most concerned questions of the public, Professor Han Ying also provided answers: 1.
What is the current prognosis of AD patients in my country? How many years can you live on average after diagnosis? Professor Han Ying: Due to the relatively backward concept of AD, ordinary people in China often seek medical attention only at the stage of moderate to severe dementia, so the prognosis is mostly unsatisfactory.
The average survival after diagnosis is only 5 to 10 years
.

If it can be diagnosed at the stage of MCI or mild AD dementia, the survival period can be significantly extended, and individual people can even reach 20 years
.

2.
What is the detection rate of AD in the preclinical stage? How to further promote the early detection of AD? Professor Han Ying: With the publicity of film and television works, the common people are no longer unfamiliar with the concept of AD, but the clinical manifestations of AD in the pre-clinical stage are still not very clear, and further popularization of science is needed
.

If the whole people have grasped the concept of AD preclinical SCD, it will not be far from early detection
.

3.
What are the important findings of your research group regarding the preclinical treatment of AD? What is the next research direction? Professor Han Ying: Our research group has been committed to the early detection of AD for a long time
.

In 2014, after Professor Jessen proposed the concept of AD preclinical SCD for the first time in the world, we actively carried out early diagnosis research for SCD, and it is now possible to make early diagnosis and differential diagnosis for SCD patients
.

However, the treatment is limited to the research situation at home and abroad, and it will not start to explore the early treatment of AD in the preclinical stage until 2021
.

 Expert profile Professor Han Ying, chief physician and doctoral supervisor of the Department of Neurology, Xuanwu Hospital of Capital Medical University, member of the MRI Committee of the Chinese Medical Association Radiology Branch, chairman of the Beijing Society of Cognitive Neuroscience, National Center for Geriatrics Clinical Medicine-China AD Chairman of the pre-clinical alliance, editorial board and reviewer of many academic journals at home and abroad
.

National Nature Review Expert
.